The Polypeptide N-acetylgalactosaminyltransferase 4 Exhibits Stage-dependent Expression in Colorectal Cancer and Affects Tumorigenesis, Invasion and Differentiation

The aberrant expression of mucin-type O-glycosylation plays important roles in cancer malignancy. The polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) are a family of conserved enzymes that initiate the mucin-type O-glycosylation in cells. In human, consistent up- or down-regulation of ppGalNAc-Ts expression during cancer development has been frequently reported. Here, we provide evidence that ppGalNAc-T4 shows a stage-dependent expression at the different stages of colorectal cancer (CRC) in the 62 pair-matched tumor/normal tissues. In detail, ppGalNAc-T4 expression is significantly induced at stage I and II but not at stage III and IV. Overexpression of ppGalNAc-T4 in CRC cells enhances colony formation and sphere formation suggesting an important role of ppGalNAc-T4 in tumorigenesis. Conversely, knockdown of ppGalNAc-T4 in CRC cells increases the cell migration and invasion, and leads to an epithelial-mesenchymal transition-like transition. Further analysis suggests that loss of ppGalNAc-T4 contributes to the dedifferentiation of CRC and high expression of ppGalNAc-T4 correlates to a good prognosis of patients. Taken together, our results not only demonstrate a stage-dependent expression of ppGalNAc-T4 in CRC progression, but also suggest that such stage-dependent expression may contribute to the tumorigenesis at the early stage and promote cell migration and invasion at the advanced stage.